Biologically Related Iron-Sulfur Chemistry

描述(申请人提供)：本申请寻求继续支持已建立的生物无机化学研究计划，该计划旨在详细了解含有铁、硫和钼、钒或镍的生物相关簇团，各种类型的簇团存在于生活的各个层面。这一建议的领域是仿生无机化学，其中建议合成某些目前在生物学中公认的最复杂的金属分配中心。这些包括在固氮酶和含镍一氧化碳脱氢酶中发现的簇，它们分别催化氮素还原为氨和一氧化碳和二氧化碳的相互转化，因此是氮、碳和氧生物利用的主要因素。主要目标是固氮酶的P-簇、含钼、钒的辅因子和全铁辅因子，以及一氧化碳脱氢酶的镍-铁-硫催化中心。提出了利用簇自组装、片段缩合和核心重排来合成这些实体的原始方法。在这项工作中准备的新的簇状物种将受到详细的物理化学表征和与适当底物的反应性调查。这项工作的一个前提是，这些生物簇的逐步形成意味着反应物本身固有的反应性性质。这项研究旨在通过展示在没有蛋白质的情况下，或者可能在蛋白质存在的情况下，什么合成路线对于构建簇实际上是可行的，从而为金属分配中心的生物合成的广泛和发展领域做出贡献。因此，精确类似物的合成可能有助于理解天然簇合物的生物合成，对于天然簇合物来说，反应途径正在慢慢显现，但分子步骤尚不清楚。与公共健康相关：拟议中的研究寻求可能与活细胞中的化学反应相似的化学反应，这些化学反应形成对生命过程和公共健康重要的含金属硫分子。这些过程包括从大气中的氮生成氨，提供用于形成DNA和许多其他生命分子的氮，以及从二氧化碳中生成一氧化碳，这一过程有助于将环境中的一氧化碳保持在有毒水平以下。要制备的分子应该有助于理解这些过程的天然催化剂是如何自然形成的。

DESCRIPTION (provided by applicant): This application seeks continued support for an established research program in bioinorganic chemistry directed at a detailed understanding of biologically relevant cluster clusters containing iron, sulfur, and molybdenum, vanadium, or nickel, various types of which are found at all levels of life. The field of this proposal is biomimetic inorganic chemistry, in which it is proposed to synthesize certain of the most complex metallocenters currently recognized in biology. These include the clusters found in nitrogenase and nickel-containing carbon monoxide dehydrogenase, which catalyse the reduction of dinitrogen to ammonia and the interconversion of carbon monoxide and carbon dioxide, respectively, and thus are major factors in the biological utilization of nitrogen, carbon, and oxygen. The main objectives are the P-cluster, molybenum- and vanadium-containing cofactors and the all-iron cofactor of nitrogenase, and the nickel- iron-sulfur catalytic center of carbon monoxide dehydrogenase. Original methods for the synthesis of these entities are proposed using cluster self-assembly, fragment condensation, and core rearrangement. New cluster species prepared in this work will be subjected to detailed physicochemical characterization and reactivity investigations with appropriate substrates. One premise of this work is that the step-by-step formation of these biological clusters implicates reactivity properties intrinsic to the reactants themselves. The research is intended to contribute to the broad and developing area of biosynthesis of metallocenters by showing what synthetic routes are actually feasible for cluster construction in the absence, and possibly in the presence, of proteins. The synthesis of accurate analogues thus may contribute to an understanding of the biosynthesis of native clusters, for which reaction pathways are slowly emerging but molecular steps are unknown. PUBLIC HEALTH RELEVANCE: The proposed research seeks chemical reactions potentially similar to those in living cells that form metal-sulfur-containing molecules of importance to life processes and public health. These processes include the formation of ammonia from atmospheric nitrogen, affording the nitrogen utilized in the formation of DNA and numerous other molecules of life, and of carbon monoxide from carbon dioxide in a process that helps maintain ambient carbon monoxide below toxic levels. The molecules to be prepared should contribute to an understanding of how nature9s catalysts for these processes area formed naturally.